The mechanisms by which drugs affect human behavior are complex, involving the interaction between the direct actions of the drug (e.g., impairment of coordination) and the functional behavioral effects such as altered motivation. Specific determinants of drug response include the drug dose, the route of administration, the person's physiological and psychological state, the particular environmental conditions, and the nature of the behavior or test being measured. One approach that we are pursuing is to vary the environmental conditions by manipulating the reinforcement (monetary) contingencies under which subjects perform various tasks. This can be thought of as manipulating a subject's motivation to perform. By also varying drug dose and using tests that measure different aspects of performance (e.g., psychomotor vs. cognitive), we can begin to explore the complex interactions underlying the effects of drugs on behavior. Another approach to investigating the mechanisms by which drugs influence behavior is to focus on performance impairment produced by psychoactive drugs. The performance-impairing effects of drugs of abuse produce a large toll on the nation each year in terms of traffic injuries and fatalities and lost productivity in the workplace. However, for most drugs, we lack basic knowledge about the behavioral mechanisms underlying their impairment of human performance. A series of studies is being conducted that will address such questions. A battery of physiological, behavioral, and performance measures designed to determine whether an individual is behaviorally impaired as the result of taking a drug has been tested with ethanol, marijuana, and cocaine. A future study will examine the effects of amphetamine, codeine, and alprazolam on this same test battery as well as a cognitive test of attention and memory. By also collecting blood samples during these studies, we will be able to gain valuable information concerning the relationship between plasma concentrations of drugs and degree of performance impairment.